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. 2023 Jun 23;21:407. doi: 10.1186/s12967-023-04209-0

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© The Author(s) 2023

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

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Fig. 3 — SIRT1 as a downstream target and negatively regulated by METTL3-mediated m6A modification in vitro and in vivo. A Volcano plots for differentially expressed mRNAs between matched oe-vector and oe-METTL3 transfected ESCs by RNA-seq. (|Fold Change|≥ 1, p < 0.001, Red point: up-regulated mRNAs, blue point: down-regulated mRNAs, the grey point indicated not differential expressed). B Volcano plots for differential methylated m6A modification transcripts between matched oe-vector and oe-METTL3 transfected ESCs by m6A epitranscriptomic microarray.(|Fold Change|≥ 1). Hyper-Up, up-regulated m6A modified mRNAs of |Fold Change|≥ 2; Hyper-Down, down-regulated m6A modified mRNAs of |Fold Change|≥ 2; Hypo-Up, up-regulated m6A modified mRNAs of |Fold Change|< 2; Hypo-Down, down-regulated m6A modified mRNAs of |Fold Change|< 2. C Venn showed SIRT1 at the intersection of RNA-seq and m6A epitranscriptomic microarray. D Top results of KEGG enrichment analysis. KEGG, Kyoto Encyclopedia of Genes and Genomes. E The m6A motif of ESCs identifified by m6A epitranscriptomic microarray. F m6A peak distribution of mRNA in m6A epitranscriptomic microarray. G The decreasing SIRT1 expression level of oe-METTL3 transfected ESCs in RNA-seq. H The increasing m6A mythylation level of oe-METTL3 transfected ESCs in m6A epitranscriptomic microarray. I The mRNA level of SIRT1 in EMs and paired tissues by RT-qPCR. J Representative IF staining of METTL3 and SIRT1 expression in Ectopic, Eutopic, and normal endometrium tissues. (Red fluorescence: METTL3; Green fluorescence: SIRT1; Blue fluorescence: DAPI; scale bar: 100 μm). K mRNA level of SIRT1 in METTL3 knockdown(up) and overexpression(down) by RT-qPCR. L Reduction enrichment level of SIRT1 in ESCs after METTL3 silencing by RIP-qPCR. M Decreasing m6A modification level of SIRT1 transcripts during METTL3 knockdown by Merip-qPCR assay. N Workflow of Endometriosis CKO mice model. O Progression of ectopic lesions (Green rectangular range) on Days 3, 5, and 7 in control and CKO-METTL3 mice. The mRNA expression of METTL3 P and volume on Days 3, 5, and 7 Q of isolated ectopic lesions were measured and analyzed. R Representative IHC images for SIRT1 in Control(up) and CKO-METTL3 group(down). (scale bars = 100 μm and 50 μm). All above result were shown in means ± SD, ns, p ≥ 0.05; *p < 0.05; **p < 0.01; ***p < 0.001